comparative effectiveness and safety of four second line pharmacological strategies in type 2 diabetes study

Conditions: Cardiovascular Events; Type2 Diabetes; Renal Disease

Summary: to perform an observational analysis to emulate a target trial (i.e., a hypothetical pragmatic trial that would have answered the causal question of interest) comparing the effectiveness and safety of sodium-glucose cotransporter-2 inhibitors (sglt2i), glucagon-like peptide 1 receptor agonists (glp-1ra), dipeptidyl peptidase-4 inhibitors (dpp-4i), and sulfonylureas (su), at the class and individual agent level, in head-to-head comparisons in patients with type 2 diabetes (t2d).

aim 1: (1a.) to evaluate the effectiveness of sodium-glucose cotransporter-2 inhibitors (sglt2i), glucagon-like peptide 1 receptor agonists (glp-1ra), dipeptidyl peptidase-4 inhibitors (dpp-4i), and sulfonylureas (su), at the class and individual agent level, in head-to-head comparisons with respect to cardiovascular (cv) events, mortality, renal events, and other patient-centered outcomes (e.g., time spent at home), in patients with t2d and moderate baseline cv risk (event rate ≤3%/year). (1b.) to examine heterogeneity in treatment effects by age, race/ethnicity, gender, levels of cv risk, including high (≥4%/year) and low risk (\<2%/year), chronic kidney disease (ckd), frailty, and multimorbidity. aim 2: (2a.) to monitor and quantify the association of the initiation of sglt2i, glp-1ra, dpp-4i, or su, at the class and individual agent level, with previously reported drug-related harms (e.g., diabetic ketoacidosis (dka), fractures, amputations, pancreatitis, severe hypoglycemia). (2b.) to scan study data sources for signals of potential serious unanticipated drug-related adverse events, using a data-mining approach (tree-based scan statistics). (2c.) by using data generated in aims 2a and 2b, to build treatment-specific outcome prediction models to identify individual patients' likelihood of drug-related harms, based on specific combinations of patient features.

Eligibility criteria:
inclusion criteria: * age ≥ 18 years for optum cliniformatics, ibm marketscan, cprd, and vha, and ≥ 65 years for medicare ffs at cohort entry * at least 12 months of continuous health plan enrollment (only claims) or registration with a general practitioner (cprd) before and including cohort entry * diagnosis of t2d within 12 months before (or ever before in cprd) and including cohort entry * low or moderate cardiovascular (cv) risk (≤3% risk of cv events/year) at cohort entry \* * metformin maintenance therapy, defined as 2 fills (or prescriptions in cprd) of metformin monotherapy recorded within 6 months before and including cohort entry exclusion criteria: * missing age or gender information * nursing care admission within 12 months before and including cohort entry (criteria ignored in cprd) * diagnosis of type 1 diabetes within 12 months before and including cohort entry * diagnosis of secondary or gestational diabetes within 12 months before and including cohort entry * any insulin fill or prescription within 12 months before and including cohort entry * diagnosis of end stage renal disease (stage ≥ 5) within 12 months before and including cohort entry * diagnosis of acute or chronic pancreatitis within 12 months before and including cohort entry * diagnosis of cirrhosis or acute hepatitis within 12 months before and including cohort entry * diagnosis of men-2 within 12 months before and including cohort entry * recorded solid organ transplant code within 12 months before and including cohort entry * patients with recorded initiation of more than one agent within a comparator class at cohort entry